The long term objective of this research is to obtain an integrated understanding of the functions and regulation of the metal-binding protein metallothionein (MT). Part of this objective is also to understand, in a very simple case, the interactions between genome and environment that insure the necessary adaptations needed by the organism and the species. In this particular case, the environmental factor under investigation is one of great, and ever increasing, importance to the health of humans and all other organisms alike: the accumulation of toxic metals such as cadmium, copper and mercury. The methods of genetics and molecular biology will be used to study the effect of different kinds of mutations of the metallothionein gene (Mtn) on the tolerance of Drosophila melanogaster to toxic metals. Some of these mutations will be obtained in vitro and re- introduced into the Drosophila genome while others will be isolated by selecting mutant individuals using traditional genetic means. Mutations will also be used to improve our understanding of the way this gene is regulated; this regulation is such that, within limits, the production of MT matches the level required to bind and "neutralize" the toxic metals present at any given moment in the organism's environment. Because of the high degree of similarity in the structure and regulation of MT in Drosophila and other species (including humans) the results of this study should go a long way toward improving our knowledge of these processes in all species.